BUMETANIDE SODIUM

Details

Stereochemistry	ACHIRAL
Molecular Formula	C17H19N2O5S.Na
Molecular Weight	386.398
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

[Na+].CCCCNC1=C(OC2=CC=CC=C2)C(=CC(=C1)C([O-])=O)S(N)(=O)=O

InChI

InChIKey=QDFGOJHAQZEYQL-UHFFFAOYSA-M

InChI=1S/C17H20N2O5S.Na/c1-2-3-9-19-14-10-12(17(20)21)11-15(25(18,22)23)16(14)24-13-7-5-4-6-8-13;/h4-8,10-11,19H,2-3,9H2,1H3,(H,20,21)(H2,18,22,23);/q;+1/p-1

HIDE SMILES / InChI

Molecular Formula	Na
Molecular Weight	22.9898
Charge	1
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Molecular Formula	C17H19N2O5S
Molecular Weight	363.408
Charge	-1
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description
Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2010/018225s024lbl.pdf
Curator's Comment: description was created based on several sources, including: http://www.rxlist.com/bumex-drug/side-effects-interactions.htm https://www.drugs.com/cdi/bumetanide.html http://www.wikidoc.org/index.php/Bumetanide_(oral)

Bumetanide is indicated for the treatment of edema associated with congestive heart failure, hepatic and renal disease, including the nephrotic syndrome. It blocks the reabsorption of sodium and fluid from the kidney's tubules. The most frequent clinical adverse reactions considered probably or possibly related to bumetanide are muscle cramps (seen in 1.1% of treated patients), dizziness (1.1%), hypotension (0.8%), headache (0.6%), nausea (0.6%) and encephalopathy (in patients with preexisting liver disease) (0.6%). One or more of these adverse reactions have been reported in approximately 4.1% of patients treated with Bumex (bumetanide). Lithium should generally not be given with diuretics (such as Bumex (bumetanide)) because they reduce its renal clearance and add a high risk of lithium toxicity. Bumex (bumetanide) may potentiate the effect of various antihypertensive drugs, necessitating a reduction in the dosage of these drugs.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Solute carrier family 12 member 2 3 Target ID: P55011 Gene ID: 6558.0 Gene Symbol: SLC12A2 Target Organism: Homo sapiens (Human) Sources: http://www.drugbank.ca/drugs/DB00887 \| https://www.ncbi.nlm.nih.gov/pubmed/16022677 \| https://www.ncbi.nlm.nih.gov/pubmed/11882915/	Inhibitor 8228	3.0 µM [IC50]
Solute carrier family 12 member 4 2 Target ID: Q9UP95\|\|\|O60632 Gene ID: 6560.0 Gene Symbol: SLC12A4 Target Organism: Homo sapiens (Human) Sources: http://www.drugbank.ca/drugs/DB00887 \| https://www.ncbi.nlm.nih.gov/pubmed/16807348	Blocker 534	60.0 µM [IC50]
Solute carrier family 12 member 5 2 Target ID: Q9H2X9 Gene ID: 57468.0 Gene Symbol: SLC12A5 Target Organism: Homo sapiens (Human) Sources: http://www.drugbank.ca/drugs/DB00887 \| https://www.ncbi.nlm.nih.gov/pubmed/16807348	Blocker 534	55.0 µM [IC50]
Solute carrier family 12 member 1 2 Target ID: Q13621 Gene ID: 6557.0 Gene Symbol: SLC12A1 Target Organism: Homo sapiens (Human) Sources: http://www.drugbank.ca/drugs/DB00887 \| https://www.ncbi.nlm.nih.gov/pubmed/26101812	Blocker 534	4.0 µM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Edema 22 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2010/018225s024lbl.pdf	Primary		Approved 8360	BUMEX Approved Use Bumetanide Injection is indicated for the treatment of edema associated with congestive heart failure, hepatic and renal disease, including the nephrotic syndrome. Almost equal diuretic response occurs after oral and parenteral administration of bumetanide. Therefore, if impaired gastrointestinal absorption is suspected or oral administration is not practical, bumetanide should be given by the intramuscular or intravenous route. Successful treatment with bumetanide following instances of allergic reactions to furosemide suggests a lack of cross-sensitivity. Launch Date 4.1523839E11

C_max

Value	Dose	Co-administered	Analyte	Population
42 ng/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/8312869	2 mg single, oral dose: 2 mg route of administration: Oral experiment type: SINGLE co-administered:		BUMETANIDE plasma	Homo sapiens population: UNKNOWN age: ADULT sex: FEMALE / MALE food status: FASTED
111.38 ng/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/22475517	2 mg single, oral dose: 2 mg route of administration: Oral experiment type: SINGLE co-administered:		BUMETANIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

AUC

Value	Dose	Co-administered	Analyte	Population
167.34 ng × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/8312869	2 mg single, oral dose: 2 mg route of administration: Oral experiment type: SINGLE co-administered:		BUMETANIDE plasma	Homo sapiens population: UNKNOWN age: ADULT sex: FEMALE / MALE food status: FASTED
258 ng × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/22475517	2 mg single, oral dose: 2 mg route of administration: Oral experiment type: SINGLE co-administered:		BUMETANIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

T_1/2

Value	Dose	Co-administered	Analyte	Population
1.88 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/22475517	2 mg single, oral dose: 2 mg route of administration: Oral experiment type: SINGLE co-administered:		BUMETANIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

F_unbound

Value	Dose	Co-administered	Analyte	Population
5% EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/22475517	2 mg single, oral dose: 2 mg route of administration: Oral experiment type: SINGLE co-administered:		BUMETANIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
3% DRUG LABEL https://nctr-crs.fda.gov/fdalabel/services/spl/set-ids/9bd7a71e-0e78-dae7-e053-2995a90ad110/spl-doc?hl=bumetanide			BUMETANIDE serum	Homo sapiens population: HEALTHY age: NEWBORN sex: UNKNOWN food status: UNKNOWN

Doses

Dose	Population	Adverse events
2 mg 2 times / day multiple, oral Recommended Dose: 2 mg, 2 times / day Route: oral Route: multiple Dose: 2 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/28291262 Page: p.4	unhealthy, 14–18 n = 21 Health Status: unhealthy Condition: Autism spectrum disorders Age Group: 14–18 Sex: M+F Population Size: 21 Sources: https://pubmed.ncbi.nlm.nih.gov/28291262 Page: p.4	Disc. AE: Hypokalemia, Anorexia... AEs leading to discontinuation/dose reduction: Hypokalemia (moderate, 14.3%) Anorexia (moderate) Fatigue (moderate) Polyuria (moderate, 4.8%) Sources: https://pubmed.ncbi.nlm.nih.gov/28291262 Page: p.4
10 mg 1 times / day multiple, oral Recommended Dose: 10 mg, 1 times / day Route: oral Route: multiple Dose: 10 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/7040493 Page: p.597	unhealthy, 22-72 n = 18 Health Status: unhealthy Condition: Renal edema Age Group: 22-72 Sex: M+F Population Size: 18 Sources: https://pubmed.ncbi.nlm.nih.gov/7040493 Page: p.597	Sources: https://pubmed.ncbi.nlm.nih.gov/7040493 Page: p.597

AEs

AE	Significance	Dose	Population
Hypokalemia	moderate, 14.3% Disc. AE	2 mg 2 times / day multiple, oral Recommended Dose: 2 mg, 2 times / day Route: oral Route: multiple Dose: 2 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/28291262 Page: p.4	unhealthy, 14–18 n = 21 Health Status: unhealthy Condition: Autism spectrum disorders Age Group: 14–18 Sex: M+F Population Size: 21 Sources: https://pubmed.ncbi.nlm.nih.gov/28291262 Page: p.4
Polyuria	moderate, 4.8% Disc. AE	2 mg 2 times / day multiple, oral Recommended Dose: 2 mg, 2 times / day Route: oral Route: multiple Dose: 2 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/28291262 Page: p.4	unhealthy, 14–18 n = 21 Health Status: unhealthy Condition: Autism spectrum disorders Age Group: 14–18 Sex: M+F Population Size: 21 Sources: https://pubmed.ncbi.nlm.nih.gov/28291262 Page: p.4
Anorexia	moderate Disc. AE	2 mg 2 times / day multiple, oral Recommended Dose: 2 mg, 2 times / day Route: oral Route: multiple Dose: 2 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/28291262 Page: p.4	unhealthy, 14–18 n = 21 Health Status: unhealthy Condition: Autism spectrum disorders Age Group: 14–18 Sex: M+F Population Size: 21 Sources: https://pubmed.ncbi.nlm.nih.gov/28291262 Page: p.4
Fatigue	moderate Disc. AE	2 mg 2 times / day multiple, oral Recommended Dose: 2 mg, 2 times / day Route: oral Route: multiple Dose: 2 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/28291262 Page: p.4	unhealthy, 14–18 n = 21 Health Status: unhealthy Condition: Autism spectrum disorders Age Group: 14–18 Sex: M+F Population Size: 21 Sources: https://pubmed.ncbi.nlm.nih.gov/28291262 Page: p.4

Overview

CYP3A4	CYP2C9	CYP2D6	hERG

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
OAT1 595 OAT3 636 OAT4 145 OAT2 144	MRP4 75 OAT3 333 OATP2 11 P-gp 1527 OAT4 76 OAT2 111

Drug as perpetrator

Target	Modality	Activity
OAT4 145	inhibitor 3240 Sources: https://pubmed.ncbi.nlm.nih.gov/14610216/	modest [IC50 348 uM]
OAT3 638	inhibitor 3240 Sources: https://pubmed.ncbi.nlm.nih.gov/14610216/	yes [IC50 0.75 uM]
OAT1 599	inhibitor 3240 Sources: https://pubmed.ncbi.nlm.nih.gov/14610216/	yes [IC50 7.6 uM]
OAT2 146	inhibitor 3240 Sources: https://pubmed.ncbi.nlm.nih.gov/14610216/	yes [IC50 77.5 uM]

Drug as victim

Target	Modality	Activity
P-gp 1527	substrate 3326 Sources: https://pubmed.ncbi.nlm.nih.gov/28192112/	no
MRP4 75	substrate 3326 Sources: https://pubmed.ncbi.nlm.nih.gov/25449033/	yes
OAT2 111	substrate 3326 Sources: https://pubmed.ncbi.nlm.nih.gov/15901346/	yes
OAT3 333	substrate 3326 Sources: https://pubmed.ncbi.nlm.nih.gov/25449033/	yes
OAT4 76	substrate 3326 Sources: https://pubmed.ncbi.nlm.nih.gov/14610216/	yes
OATP2 11	substrate 3326 Sources: https://pubmed.ncbi.nlm.nih.gov/25449033/	yes

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:3213	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:3213
ChemicalBook	CB9382992	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB9382992
MolPort	MolPort-003-666-390	https://www.molport.com/shop/molecule-link/MolPort-003-666-390
Selleck Chemicals	Bumetanide	http://www.selleckchem.com/products/Bumetanide.html
ZINC	ZINC000003813061	http://zinc15.docking.org/substances/ZINC000003813061
eMolecules	535080	https://www.emolecules.com/cgi-bin/more?vid=535080

PubMed

Title	Date	PubMed
Functional comparison of the K+-Cl- cotransporters KCC1 and KCC4.	2000 Sep 29	10913127
External Cl(-)-dependent formation of watery vacuoles by long-term hypotonic shock in 3T3-L1 cells.	2001	11832656
Diuretic therapy and resistance in congestive heart failure.	2001	11805380
Effect of chloride channel blockers on anti-IgE-stimulated histamine and IL-4/IL-13 release from human basophils.	2001 Apr	11411600
Insulin increases the turnover rate of Na+-K+-ATPase in human fibroblasts.	2001 Apr	11245608
Effects of thiazide- and loop-diuretics, alone or in combination, on calcitropic hormones and biochemical bone markers: a randomized controlled study.	2001 Aug	11489064
"Avian-type" renal medullary tubule organization causes immaturity of urine-concentrating ability in neonates.	2001 Aug	11473651
Protection of ischemic myocardium in diabetics by inhibition of electroneutral Na+-K+-2Cl- cotransporter.	2001 Aug	11454552
Insulin-independent, MAPK-dependent stimulation of NKCC activity in skeletal muscle.	2001 Aug	11448861
Cl(-)-dependent secretory mechanisms in isolated rat bile duct epithelial units.	2001 Aug	11447024
Contractile regulation of the Na(+)-K(+)-2Cl(-) cotransporter in vascular smooth muscle.	2001 Aug	11443057
Optical method for quantifying rates of mucus secretion from single submucosal glands.	2001 Aug	11435221
Regional differences in ciliary epithelial cell transport properties.	2001 Aug 1	11547344
Contribution of the Na-K-Cl cotransporter on GABA(A) receptor-mediated presynaptic depolarization in excitatory nerve terminals.	2001 Aug 15	11487619
Cisplatin-induced apoptosis of mesothelioma cells is affected by potassium ion flux modulator amphotericin B and bumetanide.	2001 Aug 15	11477563
An integrative, in situ approach to examining K+ flux in resting skeletal muscle.	2001 Dec	11824943
Growth factors stimulate the Na-K-2Cl cotransporter NKCC1 through a novel Cl(-)-dependent mechanism.	2001 Dec	11698253
Adrenergic receptor activated ion transport in human fetal retinal pigment epithelium.	2001 Jan	11133877
Hepatic uptake of synthetic chlorogenic acid derivatives by the organic anion transport proteins.	2001 Jan	11123367
Liquid and ion transport by fetal airway and lung epithelia of mice deficient in sodium-potassium-2-chloride transporter.	2001 Jul	11472970
Na+-K+-Cl- cotransporter in rat focal cerebral ischemia.	2001 Jun	11488540
cAMP-dependent fluid secretion in rat inner medullary collecting ducts.	2001 Jun	11352842
Na+ reabsorption in cultured rat epididymal epithelium via the Na+/nucleoside cotransporter.	2001 Mar	11207189
Inhibition of Na(+)/K(+)-atpase by endothelin-1 in human nonpigmented ciliary epithelial cells.	2001 Mar	11181930
HCO3- potentiates the cAMP-dependent secretory response of the human distal colon through a DIDS-sensitive pathway.	2001 May	11417223
Diverging effects of 5-HT3 receptor antagonists ondansetron and granisetron on estramustine-inhibited cellular potassium transport.	2001 May	11393584
Pulmonary oedema after ophthalmic regional anaesthesia in an unfasted patient undergoing elective surgery.	2001 May	11350330
Role of renocortical cyclooxygenase-2 for renal vascular resistance and macula densa control of renin secretion.	2001 May	11316844
Identification and characterization of human organic anion transporter 3 expressing predominantly in the kidney.	2001 May	11306713
Localization of a Na(+)-K(+)-2Cl(-) cotransporter in the rabbit lens.	2001 Nov	11747367
Role of Cl- current in endothelin-1-induced contraction in rabbit basilar artery.	2001 Nov	11668078
Vacuolation induced by VacA toxin of Helicobacter pylori requires the intracellular accumulation of membrane permeant bases, Cl(-) and water.	2001 Nov 23	11728476
Ion transport and ligand binding by the Na-K-Cl cotransporter, structure-function studies.	2001 Oct	11913460
Mechanism(s) of chloride transport in human distal colonic apical membrane vesicles.	2001 Oct	11680599
Quantitative determination of the loop diuretic bumetanide in urine and pharmaceuticals by high-performance liquid chromatography with amperometric detection.	2001 Oct	11669367
Indirectly gated Cl(-)-dependent Cl(-) channels sense physiological changes of extracellular chloride in the leech.	2001 Oct	11600643
Contribution of the Na(+)-K(+)-2Cl(-) cotransporter (NKCC1) to transepithelial transport of H(+), NH(4)(+), K(+), and Na(+) in rat outer medullary collecting duct.	2002 Apr	11912241
Chloride transport in rabbit esophageal epithelial cells.	2002 Apr	11897626
Manipulation of chloride flux affects histamine-induced contraction in rabbit basilar artery.	2002 Apr	11893580
Activation of ion secretion via proteinase-activated receptor-2 in human colon.	2002 Feb	11804840
Intrinsic optical signals in the rat optic nerve: role for K(+) uptake via NKCC1 and swelling of astrocytes.	2002 Feb	11754210
Basolateral PAR-2 receptors mediate KCl secretion and inhibition of Na+ absorption in the mouse distal colon.	2002 Feb 15	11850514
Effects of butyrate on active sodium and chloride transport in rat and rabbit distal colon.	2002 Feb 15	11850510
Cyclic AMP-dependent Cl secretion is regulated by multiple phosphodiesterase subtypes in human colonic epithelial cells.	2002 Jan 15	11891572

Patents

Sample Use Guides

In Vivo Use Guide

The usual total daily dosage of Bumetanide is 0.5 mg to 2 mg and in most patients is given as a single dose.

Route of Administration: Other

In Vitro Use Guide

10 uM of bumetanide reduced amplitude and frequency of ictal-like events (ILE) induced by 8.5 mM K(+), but it increased the frequency of ILE induced by 1 microM kainate.

Substance Class	Chemical Created by `admin` on `Thu Jul 06 18:37:45 UTC 2023` Edited by `admin` on `Thu Jul 06 18:37:45 UTC 2023`
Record UNII	1QC8KM52D1
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

BUMETANIDE SODIUM

Common Name

English

BUMETANIDE SODIUM SALT

Common Name

English

SODIUM 3-(AMINOSULFONYL)-5-(BUTYLAMINO)-4-PHENOXYBENZOATE

Systematic Name

English

BENZOIC ACID, 3-(AMINOSULFONYL)-5-(BUTYLAMINO)-4-PHENOXY-, SODIUM SALT (1:1)

Systematic Name

English

Code System Code Type Description

EPA CompTox

DTXSID60182634